Abstract

Matrix metalloproteinases (MMPs) are involved in placental remodelling throughout pregnancy. Diabetes mellitus induces alterations in tissue production of NO, a regulator of MMPs activity. The present work evaluates placental and fetal MMPs and NO levels during midpregnancy in neonatal streptozotocin-induced diabetic rats. MMP-2 and MMP-9 immunolabelling was increased both in the labyrinth zone ( p < 0.001) and in the giant trophoblast cells of the junctional zone ( p < 0.001) from diabetic placenta, when compared with controls. Also MMP-2 ( p < 0.01) and MMP-9 ( p < 0.005) activities were increased in both maternal and fetal sides of diabetic placenta when related to controls. In both sides of the diabetic placenta, nitrate/nitrite concentrations (which indicate NO production) were higher than in controls ( p < 0.05). An intense immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was found in both labyrinth ( p < 0.001) and junctional zones ( p < 0.001) of diabetic placenta. Enhanced MMP-2 activity ( p < 0.05) and NO production were also higher in the fetuses from diabetic rats when compared to controls ( p < 0.005). These findings demonstrate alterations in MMPs and NO in the feto-placental unit of diabetic rats, anomalies that are likely to be involved in the developmental alterations induced by maternal diabetes.